Application des techniques physiques, géochimiques et isotopiques pour l'évaluation de l'infiltration sous climat tempéré

Depuis plusieurs années, la Zone Non Saturée d'une parcelle expérimentale au nord de l'Italie (plaine du Pô) a fait l'objet de nombreuses études sur les caractéristiques physiques et géologiques du milieu, ainsi que sur les modalités du mouvement des eaux d'infiltration. Le site a été équipé de 6 tensiomètres à mercure, 6 bougies poreuses pour l'échantillonnage de l'eau et d'un tube d'accès pour la sonde à neutrons.L'application des différentes méthodes d'évaluation a fourni, pour la période d'étude (Septembre 1994-Août 1995), des valeurs de l'infiltration sensiblement différentes. La méthode physique, basée sur le calcul du bilan hydrique annuel, et considérant le sol comme un unique réservoir monocouche, a indiqué que 19% du total des précipitations arrive à s'infiltrer. D'autre part, un modèle de simulation intégrant les caractéristiques hydrodynamiques du sol a permis d'évaluer la recharge à 29% des précipitations annuelles. Le calcul de la répartition de la teneur en eau sur le profil porte sur la description des fluctuations temporelles du plan de flux nul, en relation avec les épisodes pluvieux et l'intensité de l'évaporation.La méthode géochimique du "profil en ions conservés" entre l'eau de pluie et du sol a permis, quant à elle, d'évaluer la lame d'eau infiltrée à environ 12% des précipitations annuelles. La composition isotopique des eaux extraites du sol manifeste un enrichissement global en isotopes lourds (2H et 18O) par rapport aux eaux météoriques, conséquence d'une évaporation intense. L'infiltration semble être de type "piston flow" dispersif. Elle suit, seulement pendant l'hiver, un flux où la composante convective dans la microporosité est prédominante sur la composante diffusive qui a lieu, de préférence, dans la macroporosité.In groundwater management, it is necessary to define water movement, evaluate infiltration and evapotranspiration rates, and quantify the physico-chemical evolution of transported solutes throughout the unsaturated zone (UZ). Traditionally, in temperate regions, recharge rate is evaluated by the comparison between physical methods (based on direct measurements of hydrological parameters with lysimeters, tensiometers and neutron gauges) and geochemical approaches (conservative ions, stable isotope profiles and artificial tracers).In the Po Plain (Northern Italy) intensive agricultural irrigation and overexploitation of groundwater profoundly affect the quality and availability of shallow groundwater resources. The region has been intensively cultivated with corn and rice during the last 5 centuries. Irrigation canals have been constructed in order to distribute water from alpine rivers to areas more favourable to agriculture. In the past, only the water balance method has been applied to obtain recharge rates in these situations.An experimental field site has been operational since 1987 in the ENEA-EUREX Nuclear Centre of Saluggia. The experimental plot represents an unsaturated zone in fluvio-glacial deposits (Holocene) of the Dora Baltea River, formed by gravel and sand, interlayered with silt levels. The water table is usually at a depth of 200 cm but it varies as a function of the river level. The objectives of the present study were to describe water movement throughout the UZ and to evaluate infiltration and evapotranspiration rates using different physico-chemical methodologies. The Saluggia plot was equipped with six tensiometers, a neutron gauge hole and 6 porous cups, up to a depth of 160 cm.During 10 years of monitoring, the most favourable period for understanding infiltration processes and water movement through the UZ is September 1994 - August 1995. This period is characterised by an exceptional rain event (300 mm in 48 hours), followed by a river flood. Water samples collected with porous cups at various depths have been analysed for chemistry and stable isotope composition, together with rainfall and Dora Baltea River water.In October 1994 (beginning of the rainy period) and May 1995 (beginning of the dry period) soil samples were collected at different depths and water was extracted under vacuum conditions. Stable isotope analyses were performed on extracted waters. Soil samples were also analysed for granulometry, chemical and mineralogical composition.Reducing soil to an unique monolayer aquifer, the water balance method suggests that only 19% of the total precipitation infiltrates, whereas a simulation model taking into account soil hydrodynamic characteristics estimates an infiltration rate of 29% of the rainfall. The position of the Zero Flux Plane (ZFP) fluctuates seasonally between the surface and the maximum studied depth, as a consequence of precipitation events and evaporation fluxes. In some periods, the ZFP is level with the water table and direct discharge may occur.Measurements of the stable isotopic composition (δ2H and δ18O) of soil water allows a quantitative estimate of direct groundwater discharge. On a δ2H versusδ18O plot, pore waters from the UZ have an isotopic composition that differs from that of the majority of groundwater samples, plotting below the local rain water line and indicating some degree of evaporation during the recharge process. The isotopic enrichment is particularly significant at the evaporation front, suggesting that pore water in soil reflects a different recharge regime from those of the regional ground waters. Water isotope and solute composition were substantially modified from their original composition during the infiltration process within the soil, via mechanisms such as anion exchange with soil particles, salt precipitation/dissolution or isotopic fractionation.Arial recharge was also evaluated using the depth distribution of a conservative solute. Assuming that chloride is derived from precipitation alone, Cl- content in soil and in rain water suggests that 12% of total rainfall infiltrates. Therefore, the recharge rate is estimated to be less than 100 mm/a. These data are in agreement with other results obtained by the chloride concentration profile method, in areas of the Po Valley, but are considerably different from those evaluated by the traditional physical methods

Aerosolization performance of jet nebulizers and biopharmaceutical aspects

In this work, 13 jet nebulizers, some of which in different configurations, were investigated in order to identify the biopharmaceutical constraints related to the quality attributes of the medicinal products, which affect their safety, efficiency, compliance, and effectiveness. The aerosolization parameters, including the aerosol output, aerosol output rate, mass median aerodynamic diameter, and fine particle fraction, were determined according to the European Standard EN 13544-1, using sodium fluoride as a reference formulation. A comparison between the aerosol output nebulization time and the fine particle fraction displayed a correlation between the aerosol quality and the nebulization rate. Indeed, the quality of the nebulization significantly increased when the rate of aerosol emission was reduced. Moreover, the performance of the nebulizers was analyzed in terms of respirable delivered dose and respirable dose delivery rate, which characterize nebulization as the rate and amount of respirable product that could be deposited into the lungs. Depending on which of these two latter parameters was used, the nebulizers showed different performances. The differences, in terms of the rate and amount of delivered aerosol, could provide relevant information for the appropriate choice of nebulizer as a function of drug product, therapy, and patient characteristics

Buona Scuola Digitale in Liguria

In questo lavoro si propone un\u2019analisi dello stato della Scuola digitale in Liguria sulla base dei dati disponibili e dell\u2019esperienza diretta di progetti condotti dagli autori. Dopo una prima parte di inquadramento del percorso di innovazione regionale nell\u2019ambito di quello nazionale, si descrive un percorso di innovazione iniziato da tempo: in una prima fase in modo sporadico e individuale, grazie soprattutto alla spinta innovativa personale di singoli dirigenti scolastici o singoli docenti, oggi grazie a progetti a cui si fa riferimento in questo lavoro in modo sempre pi\uf9 condiviso e coordinato

Candidate Genes and MiRNAs Linked to the Inverse Relationship Between Cancer and Alzheimer’s Disease: Insights From Data Mining and Enrichment Analysis

The incidence of cancer and Alzheimer\u2019s disease (AD) increases exponentially with age. A growing body of epidemiological evidence and molecular investigations inspired the hypothesis of an inverse relationship between these two pathologies. It has been proposed that the two diseases might utilize the same proteins and pathways that are, however, modulated differently and sometimes in opposite directions. Investigation of the common processes underlying these diseases may enhance the understanding of their pathogenesis and may also guide novel therapeutic strategies. Starting from a text-mining approach, our in silico study integrated the dispersed biological evidence by combining data mining, gene set enrichment, and protein-protein interaction (PPI) analyses while searching for common biological hallmarks linked to AD and cancer. We retrieved 138 genes (ALZCAN gene set), computed a significant number of enriched gene ontology clusters, and identified four PPI modules. The investigation confirmed the relevance of autophagy, ubiquitin proteasome system, and cell death as common biological hallmarks shared by cancer and AD. Then, from a closer investigation of the PPI modules and of the miRNAs enrichment data, several genes (SQSTM1, UCHL1, STUB1, BECN1, CDKN2A, TP53, EGFR, GSK3B, and HSPA9) and miRNAs (miR-146a-5p, MiR-34a-5p, miR-21-5p, miR-9-5p, and miR-16-5p) emerged as promising candidates. The integrative approach uncovered novel miRNA-gene networks (e.g., miR-146 and miR-34 regulating p62 and Beclin1 in autophagy) that might give new insights into the complex regulatory mechanisms of gene expression in AD and cancer

Fear of covid-19 for individuals and family members: Indications from the national cross-sectional study of the epicovid19 web-based survey

The study analyzed the association of the fear of contagion for oneself and for family members (FMs) during the first wave of the COVID-19 pandemic, with demographic and socioeconomic status (SES) and health factors. The study was performed within the EPICOVID19 web-based Italian survey, involving adults from April–June 2020. Out of 207,341 respondents, 95.9% completed the questionnaire (60% women with an average age of 47.3 vs. 48.9 years among men). The association between fear and demographic and SES characteristics, contacts with COVID-19 cases, nasopharyngeal swab, self-perceived health, flu vaccination, chronic diseases and specific symptoms was analyzed by logistic regression model; odds ratios adjusted for sex, age, education and occupation were calculated (aORs). Fear for FMs prevailed over fear for oneself and was higher among women than men. Fear for oneself decreased with higher levels of education and in those who perceived good health. Among those vaccinated for the flu, 40.8% responded they had feelings of fear for themselves vs. 34.2% of the not vaccinated. Fear increased when diseases were declared and it was higher when associated with symptoms such as chest pain, olfactory/taste disorders, heart palpitations (aORs > 1.5), lung or kidney diseases, hypertension, depression and/or anxiety. Trends in fear by region showed the highest percentage of positive responses in the southern regions. The knowledge gained from these results should be used to produce tailored messages and shared public health decisions

PCSK9 induces a pro-inflammatory response in macrophages.

Intraplaque release of inflammatory cytokines from macrophages is implicated in atherogenesis by inducing the proliferation and migration of media smooth muscle cells (SMCs). PCSK9 is present and released by SMCs within the atherosclerotic plaque but its function is still unknown. In the present study, we tested the hypothesis that PCSK9 could elicit a pro-inflammatory effect on macrophages. THP-1-derived macrophages and human primary macrophages were exposed to different concentrations (0.250\u2009\uf7\u20092.5\u2009\ub5g/ml) of human recombinant PCSK9 (hPCSK9). After 24\u2009h incubation with 2.5\u2009\ub5g/ml PCSK9, a significant induction of IL-1\u3b2, IL-6, TNF-\u3b1, CXCL2, and MCP1 mRNA, were observed in both cell types. Co-culture of THP-1 macrophages with HepG2 overexpressing hPCSK9 also showed the induction of TNF-\u3b1 (2.4\u2009\ub1\u20090.5 fold) and IL-1\u3b2 (8.6\u2009\ub1\u20091.8 fold) mRNA in macrophages. The effect of hPCSK9 on TNF-\u3b1 mRNA in murine LDLR-/- bone marrow macrophages (BMM) was significantly impaired as compared to wild-type BMM (4.3\u2009\ub1\u20091.6 fold vs 31.1\u2009\ub1\u20096.1 fold for LDLR-/- and LDLR+/+, respectively). Finally, a positive correlation between PCSK9 and TNF-\u3b1 plasma levels of healthy adult subjects (males 533, females 537) was observed (B\u2009=\u20098.73, 95%CI 7.54\u2009\uf7\u20099.93, p\u2009<\u20090.001). Taken together, the present study provides evidence of a pro-inflammatory action of PCSK9 on macrophages, mainly dependent by the LDLR

Patterns of novel alleles and genotype/phenotype correlations resulting from the analysis of 108 previously undetected mutations in patients affected by neurofibromatosis type I

Neurofibromatosis type I, a genetic disorder due to mutations in the NF1 gene, is characterized by a high mutation rate (about 50% of the cases are de novo) but, with the exception of whole gene deletions associated with a more severe phenotype, no specific hotspots and few solid genotype/phenotype correlations. After retrospectively re-evaluating all NF1 gene variants found in the diagnostic activity, we studied 108 patients affected by neurofibromatosis type I who harbored mutations that had not been previously reported in the international databases, with the aim of analyzing their type and distribution along the gene and of correlating them with the phenotypic features of the affected patients. Out of the 108 previously unreported variants, 14 were inherited by one of the affected parents and 94 were de novo. Twenty-nine (26.9%) mutations were of uncertain significance, whereas 79 (73.2%) were predicted as pathogenic or probably pathogenic. No differential distribution in the exons or in the protein domains was observed and no statistically significant genotype/phenotype correlation was found, confirming previous evidences

Effects of PCSK9 inhibitors on HDL cholesterol efflux and serum cholesterol loading capacity in familial hypercholesterolemia subjects: a multi-lipid-center real-world evaluation

Proprotein convertase subtilisin/kexin type 9 (PCSK9), beyond regulating LDL cholesterol (LDL-c) plasma levels, exerts several pleiotropic effects by modulating lipid metabolism in extrahepatic cells such as macrophages. Macrophage cholesterol homeostasis depends on serum lipoprotein functions, including the HDL capacity to promote cell cholesterol efflux (CEC) and the serum capacity to promote cell cholesterol loading (CLC). The aim of this observational study was to investigate the effect of PCSK9 inhibitors (PCSK9-i) treatment on HDL-CEC and serum CLC in patients with familial hypercholesterolemia (FH). 31 genetically confirmed FH patients were recruited. Blood was collected and serum isolated at baseline and after 6 months of PCSK9-i treatment. HDL-CEC was evaluated through the main pathways with a radioisotopic cell-based assay. Serum CLC was assessed fluorimetrically in human THP-1 monocyte-derived macrophages. After treatment with PCSK9-i, total cholesterol and LDL-c significantly decreased (−41.6%, p < 0.0001 and −56.7%, p < 0.0001, respectively). Total HDL-CEC was not different between patients before and after treatment. Conversely, despite no changes in HDL-c levels between the groups, ABCG1 HDL-CEC significantly increased after treatment (+22.2%, p < 0.0001) as well as HDL-CEC by aqueous diffusion (+7.8%, p = 0.0008). Only a trend towards reduction of ABCA1 HDL-CEC was observed after treatment. PCSK9-i significantly decreased serum CLC (−6.6%, p = 0.0272). This effect was only partly related to the reduction of LDL-c levels. In conclusion, PCSK9-i treatment significantly increased HDL-CEC through ABCG1 and aqueous diffusion pathways and reduced the serum CLC in FH patients. The favorable effect of PCSK9-i on functional lipid profile could contribute to the cardiovascular benefit of these drugs in FH patients

Validation of Advanced Computer Codes for VVER Technology: LB-LOCA Transient in PSB-VVER Facility

The OECD/NEA PSB-VVER project provided unique and useful experimental data for code validation from PSB-VVER test facility. This facility represents the scaled-down layout of the Russian-designed pressurized water reactor, namely, VVER-1000. Five experiments were executed, dealing with loss of coolant scenarios (small, intermediate, and large break loss of coolant accidents), a primary-to-secondary leak, and a parametric study (natural circulation test) aimed at characterizing the VVER system at reduced mass inventory conditions. The comparative analysis, presented in the paper, regards the large break loss of coolant accident experiment. Four participants from three different institutions were involved in the benchmark and applied their own models and set up for four different thermal-hydraulic system codes. The benchmark demonstrated the performances of such codes in predicting phenomena relevant for safety on the basis of fixed criteria